Monotherapy versus combination therapy against nonbacteremic carbapenem-resistant gram-negative infections: a retrospective observational study
Abdul Ghafur, T. Raja, M. A. Raja, S. G. Raman, Balaji Venkatachalam
Colistin-based combination therapy, colistin monotherapy, New Delhi metallo-beta-lactamase, extensively drug resistant, Gram-negative bacteria
Citation Information :
Ghafur A, Raja T, Raja MA, Raman SG, Venkatachalam B. Monotherapy versus combination therapy against nonbacteremic carbapenem-resistant gram-negative infections: a retrospective observational study. Indian J Crit Care Med 2017; 21 (12):825-829.
Background: Superiority of colistin–carbapenem combination therapy (CCCT) over colistin monotherapy (CMT) against carbapenem-resistant Gram-negative bacterial (CRGNB) infections is not conclusively proven.
Aim: The aim of the current study was to analyze the effectiveness of both strategies against CRGNB nonbacteremic infections.
Design: This was a retrospective observational cohort study.
Subjects and Methods: Case record analysis of patients who had CRGNB nonbacteremic infections identified over a period of 4 years (January 2012–December 2015) was done by medical record review at a tertiary care center in India. Statistical Analysis: P < 0.05 was considered as significant. Multivariate analysis was performed using Cox regression.
Results: Out of 153 patients (pneumonia 115, urinary tract infection 17, complicated skin and soft-tissue infection 18, intra-abdominal infection 1, and meningitis 2), 92 patients received CCCT and 61 received CMT. Univariate analysis revealed higher Acute Physiology and Chronic Health Evaluation II (APACHE II) score, pneumonia as the diagnosis, and Klebsiella as the causative organism to be the risk factors for higher 28-day mortality (P = 0.036, 0.006, 0.016, respectively). Combination therapy had no significant impact on mortality (odds ratio [OR] = 0.91, 95% confidence interval [CI] = 0.327–2.535, P = 0.857). Multivariate analysis revealed that higher APACHE II score and infection due to Klebsiella were found to be independent risk factors for higher mortality (OR = 3.16 and 4.9, 95% CI = 1.34–7.4 and 2.19–11.2, P = 0.008 and 0.0001, respectively).
Conclusions: In our retrospective single-center series of CRGNB nonbacteremic infections, CCCT was not superior to CMT. Multicenter large observational studies or prospective randomized clinical trials are the need of the hour.
Kim YJ, Kim SI, Hong KW, Kim YR, Park YJ, Kang MW, et al. Risk factors for mortality in patients with carbapenem-resistant Acinetobacter baumannii bacteremia: Impact of appropriate antimicrobial therapy. J Korean Med Sci 2012;27:471-5.
Andria N, Henig O, Kotler O, Domchenko A, Oren I, Zuckerman T, et al. Mortality burden related to infection with carbapenem-resistant gram-negative bacteria among haematological cancer patients: A retrospective cohort study. J Antimicrob Chemother 2015;70:3146-53.
Ghafur A, Mathai D, Muruganathan A, Jayalal JA, Kant R, Chaudhary D, et al. The Chennai declaration: A roadmap to tackle the challenge of antimicrobial resistance. Indian J Cancer 2013;50:71-3.
Falagas ME, Lourida P, Poulikakos P, Rafailidis PI, Tansarli GS. Antibiotic treatment of infections due to carbapenem-resistant enterobacteriaceae: Systematic evaluation of the available evidence. Antimicrob Agents Chemother 2014;58:654-63.
Tumbarello M, Viale P, Viscoli C, Trecarichi EM, Tumietto F, Marchese A, et al. Predictors of mortality in bloodstream infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae: Importance of combination therapy. Clin Infect Dis 2012;55:943-50.
Qureshi ZA, Paterson DL, Potoski BA, Kilayko MC, Sandovsky G, Sordillo E, et al. Treatment outcome of bacteremia due to KPC-producing Klebsiella pneumoniae: Superiority of combination antimicrobial regimens. Antimicrob Agents Chemother 2012;56:2108-13.
Daikos GL, Tsaousi S, Tzouvelekis LS, Anyfantis I, Psichogiou M, Argyropoulou A, et al. Carbapenemase-producing Klebsiella pneumoniae bloodstream infections: Lowering mortality by antibiotic combination schemes and the role of carbapenems. Antimicrob Agents Chemother 2014;58:2322-8.
Falagas ME, Rafailidis PI, Ioannidou E, Alexiou VG, Matthaiou DK, Karageorgopoulos DE, et al. Colistin therapy for microbiologically documented multidrug-resistant gram-negative bacterial infections: A retrospective cohort study of 258 patients. Int J Antimicrob Agents 2010;35:194-9.
Zarkotou O, Pournaras S, Tselioti P, Dragoumanos V, Pitiriga V, Ranellou K, et al. Predictors of mortality in patients with bloodstream infections caused by KPC-producing Klebsiella pneumoniae and impact of appropriate antimicrobial treatment. Clin Microbiol Infect 2011;17:1798-803.
Lee GC, Burgess DS. Treatment of Klebsiella pneumoniae carbapenemase (KPC) infections: A review of published case series and case reports. Ann Clin Microbiol Antimicrob 2012;11:32.
Paul M, Carmeli Y, Durante-Mangoni E, Mouton JW, Tacconelli E, Theuretzbacher U, et al. Combination therapy for carbapenem-resistant gram-negative bacteria. J Antimicrob Chemother 2014;69:2305-9.
Ghafur AK, Vidyalakshmi PR, Kannaian P, Balasubramaniam R. Clinical study of carbapenem sensitive and resistant gram-negative bacteremia in neutropenic and nonneutropenic patients: The first series from India. Indian J Cancer 2014;51:453-5.
Tumbarello M, Trecarichi EM, De Rosa FG, Giannella M, Giacobbe DR, Bassetti M, et al. Infections caused by KPC-producing Klebsiella pneumoniae: Differences in therapy and mortality in a multicentre study. J Antimicrob Chemother 2015;70:2133-43.
Gutiérrez-Gutiérrez B, Salamanca E, de Cueto M, Hsueh PR, Viale P, Paño-Pardo JR, et al. Effect of appropriate combination therapy on mortality of patients with bloodstream infections due to carbapenemase-producing enterobacteriaceae (INCREMENT): A retrospective cohort study. Lancet Infect Dis 2017;17:726-34.
Shah PG, Shah SR. Treatment and outcome of carbapenem-resistant gram-negative bacilli blood-stream infections in a tertiary care hospital. J Assoc Physicians India 2015;63:14-8.
Porwal R, Gopalakrishnan R, Rajesh NJ, Ramasubramanian V. Carbapenem resistant gram-negative bacteremia in an Indian Intensive Care Unit: A review of the clinical profile and treatment outcome of 50 patients. Indian J Crit Care Med 2014;18:750-3.
Kazi M, Shetty A, Rodrigues C. The carbapenemase menace: Do dual mechanisms code for more resistance? Infect Control Hosp Epidemiol 2015;36:116-7.